1. Field of the Invention
The present invention generally relates to low molecular weight alginate and/or pectin compositions and methods of using the same. The low molecular weight alginate and/or pectin compositions, which bind to various agents, including disease agents, heavy metals and other substances, protect mammals from and treat mammals with diseases and conditions. The low molecular weight alginate and/or pectin compositions are particularly useful in removal of deleterious agents or deleterious amounts of indigenous agents from a patient's blood supply and are therefore useful in heavy metal and environmental toxin removal as well as in calcium and cholesterol removal for treatment of arteriosclerosis.
2. Background of the Technology
It is well known that gelling agents may be effective in binding to a variety of substances, in vitro. While high molecular weight binding substances are known, due to their size, it is difficult for such substances to pass various blood barriers, including the gut or to circulate freely in the bloodstream. This is also, in part, because their solubility in water is generally too low.
Cancer metastasis is a stage of cancer which frequently marks conversion to an incurable disease. Most cancers share the ability to metastasize. In the metastatic process, cancer cells depart from the primary tumor, invade the basement membrane, traverse the bloodstream as tumor cell emboli and interact with the vascular endothelium of the target organ. There, the cancer cells proliferate to form secondary colonies. Kohn, Anti-Cancer Res., 13:2553–2259 (1993). It has been demonstrated that oral administration of modified citrus pectin, i.e., low molecular weight pectin, may be effective in suppressing or preventing metastases, by binding to residues on cancer cell surfaces, presumably through interaction between galactosyl residues on the modified pectin with surface galectin-3, a carbohydrate binding protein on the surface of cancer cells. Pienta, et al., J. Nat. Cancer Inst. 87, 348–353 (1995). It has also been demonstrated in application Ser. No. 09/255,265 that like modified pectin, modified alginate is effective in preventing and/or treating the metastatic process.
Cancer cells are not the only inimical elements circulating in mammalian blood. In many cases, diseases and/or conditions are mediated by circulating inorganic and/or organic agents. Thus, deleterious agents or even increased amounts of indigenous substances can induce such diseases or conditions. For example, calcium has been associated with a number of disease conditions, including arteriosclerosis and calcinosis. Arteriosclerosis is also influenced by the presence of cholesterol in the bloodstream.
While there are a variety of treatments for removal of detrimental amounts of circulating agents such as heavy metals, typically, these embrace removal, and treatment of portions of a patient's blood supply and reintroduction to the patient.
Algin and pectin, or alignates or pectinates digestion products of each, are known gelling agents. Algins and pectins occur naturally; a chief source of algins is seaweed; a chief source of pectins is citrus. Alginates are formed by a mixture of polymannuronic acid and polyguluronic acid. Repeating sub-units are bound by glycosidic links at the 1a–4a-di-axial position (polyguluronic acid) while repeating sub-units of polymannuronic acid are bound by galactic links at the 1e–4e diequatorial position. Pectins are polymers of galacturonic acid that may be partially esterified. Naturally occurring algins and naturally occurring pectins are high molecular weight products. Both can, however, be reduced to low molecular weight products (defined herein as 40,000 daltons or less) by either chemical treatment (e.g., alkaline hydrolysis) or enzymatic degradation.
Alginates generally have superior protein recovery rates when compared to pectins of relatively similar molecular weight. Clare, Industrial Gums (1993 3rd Edition). Alginates therefore may exhibit a stronger binding ability than pectins for many substances.
Besides binding cancer cells, alginates are known to be effective metal binding compounds. This, along with the superior recovery rate associated with alginates, lends support that alginates would be useful in the prevention and/or treatment of diseases and/or conditions.
U.S. Pat. No. 5,141,927 discloses the use of an alginate and vitamin D composition to treat hypertension.
U.S. Pat. No. 5,597,810 discloses the use of an alginate-cholesterol compound to attract undesired lipids in the fluid media of the digestive tract prior to their absorption across cells lining the tract.
U.S. Pat. Nos. 5,283,086 and 5,324,526 disclose an algin-containing food or beverage as a source of dietary fiber. The patents disclose that the algin-containing food or beverage, which contains an aqueous solution of an algin having a weight average molecular weight in the range from about 10,000 to about 150,000, can be used to suppress the absorption of harmful substances in the digestive tract.
Japanese Patent No. 09235234 (Abstract) discloses the use of alginate oligosaccharides in the intestine to treat hyperlipidemia and arteriosclerosis.
Kimura et al., J. Ethnopharmacol, 54(1):47–54 (1996) (Abstract), discloses a study of natural sodium alginate (AG-270 (i.e., 2,700 kDa)) and three low-molecular weight sodium alginates (AG-1 (10 kDa), AG-5 (50 kDa) and AG-10 (100 kDa)) on cholesterol excretion and glucose tolerance in rats. Kimura et al. discloses that the study revealed that the natural sodium alginate and two of the three modified sodium alginates enhanced cholesterol secretion and inhibited blood glucose levels from rising after glucose administration. The authors noted that the results suggest that the effects of natural sodium alginate and AG-5 and AG- 10 on cholesterol excretion and glucose tolerance may be due to inhibition of cholesterol and glucose adsorption from the small intestine by gelling of free alginic acid converted in the stomach and that these alginates can be used in the treatment/prevention of obesity, hypercholesterolemia and diabetes.
None of the references discussed above disclose substances that bind deleterious agents or deleterious amounts of indigenous agents in the bloodstream. In particular, none of the references discussed above disclose substances that are able to be absorbed through the intestinal mucosa, enter the bloodstream and exert their effects. In addition, none of the references discussed above disclose chelation and removal of heavy metals. Accordingly, there is a need to provide a composition and method by which disease and/or conditions caused by deleterious agents or deleterious amounts of indigenous agents circulating in the bloodstream can be prevented or reduced.
It is an object of the invention to provide a safe and effective treatment for high circulating amounts of detrimental agents such as heavy metals and environmental toxins.
It is an additional object of the invention to provide a safe and effective treatment for high circulating amounts of indigenous agents such as calcium and other minerals which contribute deposits such as calcinosis (large calcium deposits present in auto-immune condition like dermatomyositis) as well as cholesterol in order to prevent and or treat atherosclerosis. A further object is to provide a method for treating arteriosclerosis with reduced side effects.